Financial Data and Key Metrics Changes - As of December 31, 2024, the company's cash and cash equivalents totaled approximately $20 million, which is expected to fund operations into the fourth quarter of 2025 [36] - The company is actively pursuing options to fund the CLS-AX Phase 3 program, including potential partnerships with third parties [36] Business Line Data and Key Metrics Changes - The company reported positive results from the ODYSSEY Phase 2b wet AMD clinical trial, leading to a successful end of Phase 2 meeting with the FDA regarding planned Phase 3 activities for CLS-AX [7][29] - The SCS Microinjector has been used for over 15,000 suprachoroidal injections, indicating strong interest from retinal specialists and pharmaceutical companies [6] Market Data and Key Metrics Changes - The wet AMD market represents over $12 billion in annual sales, with the company positioning CLS-AX as a maintenance treatment to capture a significant share [31] - The company’s partner, Arctic Vision, achieved regulatory milestones in the Asia-Pacific region, with product approvals in Australia and Singapore, and a new drug application under review in China [9] Company Strategy and Development Direction - The company aims to maximize the commercial potential of CLS-AX through a pivotal Phase 3 program designed to reduce regulatory risk and enhance market competitiveness [29][30] - The strategy includes targeting treatment-naive patients to potentially expand the commercial value of CLS-AX [20] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the Phase 3 trial design and its potential to demonstrate the efficacy of CLS-AX, emphasizing the importance of reducing variability in patient selection [29][84] - The company is optimistic about the broad applicability of suprachoroidal delivery in treating serious retinal diseases, with ongoing evaluations of small molecules for geographic atrophy [32] Other Important Information - The company is the only TKI in development with multi-dosing data from its Phase 2b trial and the ability to re-dose before six months, which is seen as a significant differentiator [29] - The company is preparing for participation in upcoming healthcare conferences to further engage with stakeholders [36] Q&A Session Summary Question: How might the amendments to the planned Phase 3 improve results from Phase 2? - Management believes that excluding patients with higher disease variability will lead to better results in the general population [45][46] Question: How long will it take to enroll the treatment-naive population? - Enrollment is expected to take around 12 months, based on recent trials [48] Question: What is the estimated cost of the Phase 3 program? - While specific costs were not disclosed, similar Phase 3 trials have been around $55 million to $60 million [55] Question: How will the redosing criteria work? - Redosing will rely on OCT biomarkers, with a focus on intraretinal fluid, and will be distinct from rescue criteria [95][100] Question: Will the inclusion criteria impact enrollment speed? - Management anticipates minimal impact on enrollment speed, estimating that less than 10% of patients would be rejected based on the new criteria [84]

Group 1 - Clearside Biomedical reported a quarterly loss of $0.10 per share, better than the Zacks Consensus Estimate of a loss of $0.13, representing an earnings surprise of 23.08% [1] - The company posted revenues of $0.31 million for the quarter ended December 2024, surpassing the Zacks Consensus Estimate by 13.33%, but down from $6.35 million year-over-year [2] - The stock has increased approximately 7.4% since the beginning of the year, contrasting with the S&P 500's decline of -2.9% [3] Group 2 - The current consensus EPS estimate for the upcoming quarter is -$0.13 on revenues of $0.2 million, and for the current fiscal year, it is -$0.54 on revenues of $5.23 million [7] - The Medical - Biomedical and Genetics industry is currently ranked in the top 28% of over 250 Zacks industries, indicating a favorable outlook compared to the bottom 50% [8]

Product Development and Approval - The company focuses on a novel suprachoroidal injection platform for targeted therapy delivery to the back of the eye, potentially improving vision in patients with sight-threatening eye diseases [20]. - The first product, XIPERE, was approved by the FDA in October 2021, marking a significant milestone as the first approved therapeutic delivered into the suprachoroidal space [21]. - The suprachoroidal injection method offers benefits such as non-surgical procedures, lower administration frequency, and improved safety profiles compared to traditional intravitreal injections [25]. - A permanent Category 1 CPT code for suprachoroidal injection was granted on January 1, 2024, which may enhance access and insurance coverage for the procedure [26]. - The clinical development pipeline includes CLS-AX, a proprietary suspension of axitinib for wet AMD, which has completed two clinical trials and is positioned for further development [38][39]. - CLS-AX has shown up to eleven times higher drug levels in affected tissues compared to intravitreal administration, indicating potential efficacy benefits [43]. - CLS-AX demonstrated a 77% - 85% reduction in treatment burden compared to the average monthly injections in the six months prior to administration [48]. - In the ODYSSEY trial, 100% of participants went 3 months without additional treatment, and 67% went 6 months before mandatory re-dosing [52]. - The ODYSSEY trial achieved primary and secondary outcomes, including mean change from baseline in BCVA and treatment burden measured by total injections [50]. - CLS-AX was well-tolerated with no serious adverse events reported throughout the 36-week trial [54]. - The company plans to initiate two pivotal Phase 3 trials in the second half of 2025, pending funding [56]. - Arctic Vision completed enrollment in a Phase 3 trial for ARCATUS in China for uveitic macular edema [66]. - Arctic Vision announced positive topline results from its Phase 3 uveitic macular edema clinical trial in China in July 2024 [66]. Financial Performance and Funding - The company incurred a net loss of $34.4 million in 2024 and $32.5 million in 2023, expecting significant expenses and operating losses in the coming years [187]. - The company has an accumulated deficit of $355.3 million as of December 31, 2024, with cash and cash equivalents of $20.0 million, raising substantial doubt about its ability to continue as a going concern [197]. - The company expects its existing cash and cash equivalents to fund operating expenses into the fourth quarter of 2025, but substantial additional funding will be needed thereafter [191]. - A registered direct offering in February 2024 raised approximately $15.0 million through the sale of 11,111,111 shares of common stock and accompanying warrants [195]. - The company has sold rights to receive certain royalty and milestone payments for up to $65 million under various license agreements, which may impact future revenue streams [196]. - The company is looking to selectively partner its proprietary technology for use with novel gene therapies to expand its development pipeline [76]. - The company relies on additional financing to achieve its business objectives, and failure to secure such financing could delay or cease drug development programs [194]. Market Potential and Competition - Approximately 20 million individuals in the U.S. aged 40 and older are affected by AMD, with a projected increase to 22 million by 2050, highlighting the market potential for effective treatments [40]. - The current anti-VEGF market for retinal diseases generated approximately $14.3 billion in global sales in 2020, underscoring the significant market opportunity [40]. - CLS-AX faces competition from established anti-VEGF drugs, including Lucentis and Avastin, which are approved for various ocular conditions [99]. - The SCS Microinjector competes with devices from Everads Therapy, Ltd and Uneedle B.V., which are in early-stage clinical development [104]. - Future competition may arise from biosimilar anti-VEGF products as they gain approval and enter the market [101]. Regulatory Environment - The FDA regulates the company's drug and device products under the Food, Drug and Cosmetic Act, which includes extensive requirements for clinical testing and approval [123]. - The clinical trial process includes three phases, with Phase 1 focusing on safety, Phase 2 on efficacy, and Phase 3 on further demonstrating clinical efficacy [128][131]. - The FDA review process for a New Drug Application (NDA) typically takes 10 months, but can be expedited to 6 months under priority review [134]. - Post-approval, the FDA imposes ongoing regulations, including requirements for recordkeeping and reporting of adverse experiences [135]. - The company may pursue development of drugs under Section 505(b)(2) NDAs, which allows reliance on existing studies for approval [141]. - The company may seek orphan drug designation for products in the future, but there is no guarantee of obtaining such designation or exclusivity [151]. - The company must comply with various regulatory requirements in foreign markets, which may differ from U.S. regulations and could involve longer approval times [152]. Intellectual Property and Licensing - The company has a robust intellectual property portfolio with 34 issued U.S. patents and over 80 international patents related to the SCS Microinjector and its applications [27]. - The patent estate includes 34 granted U.S. patents and 21 pending applications, with expiration dates ranging from 2027 to 2042 [109]. - The BioCryst License Agreement will expire upon the expiration of the royalty term in each country, with specific termination rights for both parties [87]. - The company has entered into a Purchase and Sale Agreement for up to $65 million, selling rights to receive royalty and milestone payments under various license agreements [89]. - The company received an upfront license fee of $5.0 million from BioCryst Pharmaceuticals for the SCS Microinjector, with potential additional payments of up to $30.0 million in clinical and regulatory milestones [86]. Compliance and Legal Risks - The federal Anti-Kickback Statute prohibits offering or receiving remuneration to induce purchases under federal healthcare programs [155]. - The federal civil False Claims Act prohibits knowingly presenting false claims for payment to the federal government [157]. - The company faces potential penalties under HIPAA for violations related to the privacy and security of protected health information [162]. - The EU GDPR imposes strict requirements for processing personal data, with fines up to €20 million or 4% of annual global revenue [163]. - The company may face significant adverse consequences if unable to lawfully transfer personal data from the EEA or UK to the U.S. [164]. - Compliance with the California Consumer Privacy Act (CCPA) and the California Privacy Rights Act (CPRA) increases compliance costs and potential liability for the company [165]. - The company faces challenges due to increased federal and state regulation of payments and transfers of value to healthcare professionals, which may impact its business operations [167]. Employment and Organizational Structure - The company has 32 full-time employees as of December 31, 2024, with no representation by labor unions [181]. - The company has incurred significant losses since inception and may never achieve or maintain profitability, with financial results expected to fluctuate significantly [187]. Risks in Drug Development - The company faces significant risks in drug development, including the uncertainty of achieving regulatory approval and market acceptance for its product candidates [210]. - Clinical drug development is lengthy and expensive, with high risks of failure, making it uncertain when or if product candidates will receive regulatory approval [215]. - Preclinical and early clinical trial outcomes may not predict later success, and many companies have failed to obtain marketing approval despite satisfactory early results [216]. - Unforeseen events during clinical trials could delay or prevent marketing approval, including acceptance by physicians and patients, competition, and reimbursement issues [217]. - Regulatory or institutional review boards may not authorize the commencement of clinical trials, leading to potential delays [218]. - The ODYSSEY trial was delayed due to FDA draft guidance, necessitating a reassessment of the original protocol design [219].

Financial Data and Key Metrics Changes - As of December 31, 2024, the company's cash and cash equivalents totaled approximately $20 million, which is expected to fund operations into the fourth quarter of 2025 [38]. Business Line Data and Key Metrics Changes - The company reported positive results from the Odyssey Phase IIb WET-AMD clinical trial, leading to a successful end-of-Phase II meeting with the FDA regarding the planned Phase III activities for CLSAX [8]. - CLSAX is positioned as a leading maintenance treatment for WET-AMD, with plans to enroll treatment-naive patients to potentially expand its commercial value [21][30]. Market Data and Key Metrics Changes - The wet AMD market represents over $12 billion in annual sales, and the company believes that CLSAX's flexible dosing regimen will provide a competitive advantage [32]. Company Strategy and Development Direction - The company is focused on advancing its small molecule superchoroidal pipeline led by CLSAX for the treatment of wet AMD, with increasing interest from retinal specialists and pharmaceutical companies [40]. - The Phase III trial design aims to reduce variability and maximize commercial potential by targeting treatment-naive patients and employing flexible dosing intervals [21][30]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the Phase III program's design and its potential to demonstrate the efficacy of CLSAX, with expectations of minimal to no anti-VEGF rescue needed during the trial [30]. - The company is actively pursuing options to fund the CLSAX Phase III program, including potential partnerships [38]. Other Important Information - The company has made significant progress with its partners in validating the applicability of superchoroidal delivery for various indications, with ongoing or planned Phase III trials in multiple territories [9][10]. Q&A Session Summary Question: How might the amendments to the Phase 3 plan improve results from Phase 2? - Management believes that excluding patients with higher variability will lead to better results in the general population, as those who did not require extra treatment performed well [47][48]. Question: How long is expected to enroll the treatment-naive population? - Enrollment is expected to take around 12 months, based on recent trials [51]. Question: What is the estimated overall cost of the Phase III program? - While specific costs were not disclosed, similar Phase III trials have been around $55 million to $60 million each [58]. Question: What are the powering assumptions in the Phase III trial? - The powering assumptions are based on a 14-letter variability, similar to other studies, with a 4.5% letter margin as suggested by the agency [94]. Question: Can you elaborate on redosing criteria and physician discretion? - Redosing criteria will rely on OCT biomarkers, with a focus on intra-retinal fluid, while rescue criteria will be based on vision loss and worsening anatomy [100][103].

Financial Data and Key Metrics Changes - As of December 31, 2024, the company's cash and cash equivalents totaled approximately $20 million, which is expected to fund operations into the fourth quarter of 2025 [27] - The company is actively pursuing options to fund the CLSAX Phase III program, including potential partnerships with third parties [27] Business Line Data and Key Metrics Changes - The SES microinjector has been used for over 15,000 suprachoroidal injections, indicating strong interest from retinal specialists and pharmaceutical companies [6] - Positive results from the Odysee Phase 2b clinical trial have led to a successful end of Phase II meeting with the FDA regarding CLSAX [6][7] Market Data and Key Metrics Changes - The wet AMD market represents over $12 billion in annual sales, highlighting the commercial potential for CLSAX [22] - The company’s partner Arctic Vision has achieved several regulatory milestones in the Asia Pacific region, with products approved in Australia and Singapore [9] Company Strategy and Development Direction - The company aims to position CLSAX as a leading maintenance treatment for wet AMD, focusing on reducing variability in clinical trial outcomes [11][21] - The Phase III trial design includes two pivotal non-inferiority trials, which are expected to maximize commercial opportunities and reduce regulatory risks [14][22] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the Phase III program's design and its potential to demonstrate the drug's efficacy and safety [39][40] - The company is optimistic about the broad applicability of suprachoroidal delivery in treating serious retinal diseases, with ongoing evaluations for additional small molecule treatments [23][25] Other Important Information - The company is preparing for participation in upcoming healthcare conferences to further engage with stakeholders [27] - The management team emphasized the importance of flexible dosing regimens in the competitive landscape of wet AMD treatments [22] Q&A Session Summary Question: How might the amendments to the planned Phase III improve results from Phase II? - Management believes that moving to a more general patient population will yield better results, as the previous Phase II focused on difficult-to-treat patients [35] Question: How long is expected to enroll the treatment-naive population? - Enrollment is expected to take around twelve months, based on recent trials [38] Question: What is the estimated overall cost of the Phase III program? - While specific costs were not disclosed, similar Phase III trials have been estimated around $55 million to $60 million [46] Question: What is the financing strategy for the Phase III study? - The company is pursuing options to fund the clinical part of the study, including potential partnerships [52] Question: Can you elaborate on the redosing criteria? - Redosing will rely on OCT biomarkers, with a focus on intra-retinal fluid, and will be scientifically justified to reduce variability [75][76]

Revenue Performance - License and other revenue for Q4 2024 was $0.3 million, a decrease of 95.2% compared to $6.3 million in Q4 2023[6] - Full year 2024 license and other revenue totaled $1.7 million, a decrease of 79.5% from $8.2 million in 2023[10] Research and Development Expenses - R&D expenses for Q4 2024 were $4.2 million, down 33.1% from $6.3 million in Q4 2023, primarily due to lower clinical trial costs[6] - R&D expenses for the full year 2024 were $18.6 million, down 10.6% from $20.8 million in 2023[10] Net Loss - Net loss for Q4 2024 was $7.3 million, or $0.10 per share, compared to a net loss of $4.8 million, or $0.08 per share, in Q4 2023[6] - Net loss for the full year 2024 was $34.4 million, or $0.47 per share, compared to a net loss of $32.5 million, or $0.53 per share, in 2023[10] Cash Position - As of December 31, 2024, cash and cash equivalents totaled $20.0 million, sufficient to fund operations into Q4 2025[6] Regulatory and Clinical Developments - Successful End-of-Phase 2 meeting with the FDA confirmed plans for Phase 3 trials of CLS-AX in wet AMD[3] - New Drug Application for ARCATUS® (XIPERE®) for uveitic macular edema accepted for review in China[3] - Multiple medical meetings highlighted the advantages of Clearside's SCS Microinjector® in retinal disease treatments[3]

Core Insights - Clearside Biomedical, Inc. has successfully completed an End-of-Phase 2 meeting with the FDA, aligning on Phase 3 plans for CLS-AX in the treatment of wet AMD [1][3] - The company’s Asia-Pacific partner, Arctic Vision, has had its New Drug Application for ARCATUS accepted for regulatory review in China [1][3] - Multiple presentations at medical meetings have highlighted the advantages of Clearside's suprachoroidal drug delivery system [1][8] Recent Developments - The FDA meeting confirmed key elements of the Phase 3 program for CLS-AX, including trial design and endpoints, based on positive Phase 2b results [3] - Arctic Vision's NDA for ARCATUS has been accepted in China, with previous approvals in Australia and Singapore [3] - Clearside's partners are advancing their suprachoroidal drug candidates into Phase 3 trials, including REGENXBIO and Aura Biosciences [3] Financial Performance - For Q4 2024, Clearside reported license and other revenue of $0.3 million, down from $6.3 million in Q4 2023 [4][5] - R&D expenses for Q4 2024 were $4.2 million, a decrease from $6.3 million in Q4 2023, attributed to lower clinical trial costs [4][5] - The net loss for Q4 2024 was $7.3 million, compared to a net loss of $4.8 million in Q4 2023 [4][5] Company Overview - Clearside Biomedical is focused on revolutionizing the delivery of therapies to the back of the eye through the suprachoroidal space, utilizing its patented SCS Microinjector [9] - The company is developing a pipeline of small molecule candidates, with its lead program, CLS-AX, targeting wet AMD [9] - Clearside has also developed XIPERE, which is commercially available in the U.S. through a partner [9]

Core Insights - Clearside Biomedical is advancing suprachoroidal drug delivery as a transformative method for treating macular diseases, with six abstracts accepted for presentation at the ARVO 2025 Meeting [1][2] Company Developments - The company’s proprietary formulation, CLS-AX, a suspension of axitinib, shows potential as a long-acting therapy for wet age-related macular degeneration (AMD), demonstrating durability and safety in clinical trials [2][5] - The SCS Microinjector allows for targeted delivery of therapeutics directly to the retina, enhancing the precision and applicability of treatments [1][6] - Clearside is planning a Phase 3 program for CLS-AX and is also evaluating other small molecules for treating geographic atrophy [7] Research and Presentations - Six abstracts related to the suprachoroidal drug delivery platform will be presented at the ARVO 2025 Meeting, covering topics such as the efficacy of CLS-AX and advancements in training models and segmentation algorithms [1][3][4] - Notable presentations include top-line results from the ODYSSEY Phase 2b study and a literature review on the evolving role of suprachoroidal drug delivery [3][4] Technology and Innovation - The SCS injection platform provides unprecedented access to the back of the eye, allowing for a non-surgical procedure that could improve patient outcomes [6][7] - The SCS Microinjector is designed with custom features to optimize drug administration, potentially reducing toxic effects on non-diseased cells [6]

Core Insights - Clearside Biomedical is advancing its lead clinical program, CLS-AX, for the treatment of neovascular age-related macular degeneration (wet AMD) through its unique suprachoroidal delivery platform [2][10] - The company emphasizes the need for more sustainable and less frequent treatment options for wet AMD, highlighting the potential benefits of its innovative delivery method [3][4] Group 1: Clinical Program and Technology - CLS-AX is a proprietary injectable suspension of axitinib, a tyrosine kinase inhibitor (TKI), designed for suprachoroidal injection, which may offer advantages over existing therapies by achieving pan-VEGF blockade [7][8] - Recent clinical trials have shown that CLS-AX is well tolerated and has a positive safety profile, with the potential for prolonged duration and targeted delivery to affected tissue layers [8][9] - The suprachoroidal injection method could reduce the risk of complications such as endophthalmitis and cataract, which are associated with traditional intravitreal therapies [4][5] Group 2: Regulatory and Market Context - The wet AMD market is significant, valued at over $12 billion, and the company is preparing for a Phase 3 clinical trial following successful discussions with the FDA [5][10] - Clearside's regulatory strategies are informed by recent FDA guidance, which will shape the development of CLS-AX and its positioning in the market [5][6] - The company aims to transform treatment options for retinal diseases through its patented SCS Microinjector, which allows for targeted and compartmentalized drug delivery [9][10]

Core Insights - Clearside Biomedical is advancing its lead clinical program, CLS-AX, for the treatment of neovascular age-related macular degeneration (wet AMD) through its innovative suprachoroidal delivery platform [1][6][9] - The company emphasizes the need for more sustainable and less frequent treatment options for wet AMD, highlighting the potential benefits of its suprachoroidal injection method [2][3] Group 1: Clinical Program and Technology - CLS-AX is a proprietary injectable suspension of axitinib, a tyrosine kinase inhibitor (TKI), designed for suprachoroidal injection, which may offer advantages over existing therapies by achieving pan-VEGF blockade [6][7] - Recent clinical trials have shown that CLS-AX is well tolerated and has a positive safety profile, with the potential for prolonged duration and targeted delivery to affected tissues [7][8] - The company is planning a Phase 3 trial for CLS-AX following a successful End-of-Phase 2 meeting with the FDA, indicating a strong regulatory strategy [3][4] Group 2: Market Context and Regulatory Strategy - The wet AMD market is significant, valued at over $12 billion, and there is a growing demand for innovative treatment options that can reduce the treatment burden on patients [4][9] - Clearside's presentations at the 2025 Wet AMD & Diabetic Eye Disease Summit highlighted the limitations of current anti-VEGF therapies and the potential of suprachoroidal delivery to transform treatment [2][3] - The company is actively engaging with the FDA to navigate the regulatory landscape for wet AMD therapies, which will inform its clinical development plans [4][9]